Purpose: To determine the safety and efficacy of a single in vivo gene transfer of the Herpes simplex thymidine kinase gene by infiltrating the surgical resection margin of the tumor with escalating doses of PA317/G1Tk1SvNa.7 vector producer cells followed 14 days later by a two week course of ganciclovir in pediatric patients with progressive or recurrent malignant supratentorial brain tumors. Study Plan: A head MRI will be obtained to assess tumor response at day 28, months 1,2,3,5,7,9,12 then every 3 months through month 24. Study endpoints will grade 3/4 adverse events for safety, and tumor response /time to progression/survival for efficacy. Significance: Gene therapy may achieve improved survival in this poor prognosis patient group, with less toxicity than conventional chemotherapy/radiation approaches, while providing data for future studies utilizing gene therapy strategies.